HER2 Positive Breast Cancer

Among patients with a solitary extracranial metastasis from breast cancer, TNBC was associated with the poorest OS and DPFS rates. Identification of other significant prognostic factors for oligometastatic breast cancer patients may inform guidelines for metastasis directed treatments.

These results suggest that SLC35A2 is overexpressed in breast cancer tissues compared to adjacent non-neoplastic tissues and may serve as a potential prognostic marker for HER2-positive subtype breast cancer. Furthermore, breast cancer patients with the HER2 positive subtype who exhibited decreased levels of SLC35A2 expression demonstrated improved long-term prognostic outcomes.

These results provide insights into the complex interactions between breast cancer cells and the surrounding microenvironment. Further research is necessary to identify the specific factors within breast cancer conditioned medium that mediate these effects and to develop targeted therapies that disrupt this interaction.

P3, N=517, Completed, Qilu Pharmaceutical Co., Ltd. | Not yet recruiting --> Completed | Trial completion date: Dec 2022 --> Oct 2023

Therapeutic results are slightly better due to the standardization of a multidisciplinary approach and the use of combined primary chemotherapy and/or targeted therapies (especially in HER2 positive patients), followed by mastectomy plus radiotherapy. The 5-year overall and disease-free survival is at more than 60%, related to an IBC mortality decrease observed in the cohorts of patients treated in the last decade.

In this study, we evaluated the association between TILs and pathological response (pCR) and invasive-disease free survival (IDFS) in 389 patients with stage II-III HER2 positive breast cancer who received neoadjuvant anthracycline-containing or anthracycline-free chemotherapy combined with trastuzumab and pertuzumab in the TRAIN-2 trial. We found no interactions between TILs and anthracycline treatment. Our results suggest that high TIL scores might be able to identify stage II-III HER2-positive breast cancer patients with a favorable prognosis.

In terms of OS, Capecitabine+Trastuzumab, Lapatinib+Trastuzumab and Pyrotinib+Capecitabine exhibited better effect compared to other treatments. Based on these findings, trastuzumab-containing regimens emerge as a preferable and recommended choice in clinical practice for managing HER2-positive breast cancer. PROSPERO, identifier CRD42023414348.

The SUVmax ratio of HER2-positive breast cancer brain metastases was significantly greater than that of HER2-negative lesions (3.98 vs 1.79, U = 38.00, p = 0.008). The SUVmax ratio may help to identify the HER2 status of breast cancer brain metastases, if validated prospectively.

P1, N=63, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=185, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Feb 2025

P1, N=33, Recruiting, Mayo Clinic | Trial completion date: Aug 2024 --> Aug 2027 | Trial primary completion date: Aug 2024 --> Aug 2027

P2, N=73, Completed, SOLTI Breast Cancer Research Group | Active, not recruiting --> Completed

P1/2, N=18, Recruiting, Jonsson Comprehensive Cancer Center | Phase classification: P1b --> P1/2 | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2025

The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.

High PFDN4 expression was associated with poor overall survival in chemotherapy and resistance to doxorubicin and paclitaxel through the CREBP1/AURKA pathway in the triple-negative MDAMB231 cell line. This study provides insightful evidence for the value of PFDN4 in poor prognosis and chemotherapy resistance in breast cancer patients.

However, unlike breast cancer, the efficacy of other anti-HER2 drugs, such as lapatinib, pertuzumab, and T-DM1, has failed to improve outcomes in advanced and locally advanced resectable GEA. Recently, the combination of trastuzumab with pembrolizumab, along with chemotherapy, and the development of trastuzumab deruxtecan, with its specific bystander activity, demonstrated improved outcomes, renewing attention in the treatment of this disease. This review will summarise historical and emerging therapies for the treatment of HER2-positive GEA, with a section dedicated to the HER2 molecular pathway and the use of novel blood biomarkers, such as circulating tumour DNA and circulating tumour cells, which may be helpful in the future to guide treatment decisions.

This article systematically reviews the latest research progress on TLSs in breast cancer and the application of machine learning in the detection of TLSs and the study of breast cancer prognosis. The insights provided contribute valuable perspectives for further exploring the biological differences among different subtypes of breast cancer and formulating personalized treatment strategies.

P2, N=257, Completed, Palleos Healthcare GmbH | Active, not recruiting --> Completed

P1, N=63, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=25, Completed, Hospital Universitario 12 de Octubre

P2, N=55, Recruiting, SOLTI Breast Cancer Research Group | Trial primary completion date: Dec 2023 --> Dec 2024

Here, we provide an updated summary of the existing both pre- and clinical studies of the role of FGFR4 in BCa, with a special focus on its contribution to subtype switching during metastatic spread and/or induced by therapy. We also discuss a potential clinical benefit of targeting FGFR4 in the development of new treatment strategies.

Metabolic profiling of lead plants revealed the existence of multiple anticancer compounds. Our study demonstrates the considerable potential of the mentioned plants as innovative therapies for HER2-positive breast cancer.

P3, N=382, Not yet recruiting, Biocon Biologics UK Ltd | Initiation date: Mar 2024 --> Sep 2024

P3, N=900, Active, not recruiting, Shanghai Henlius Biotech | Recruiting --> Active, not recruiting

After intraventricular administration in rats, we demonstrated that the brain-to-blood efflux of Fab was up to 10 times lower than for trastuzumab, associated with a two-fold higher brain penetration compared to trastuzumab. This Fab, capable of significantly reducing brain-to-blood efflux and enhancing brain penetration after intra-cerebrospinal fluid injection, could thus be a new and original effective drug in the treatment of HER2 breast cancer brain metastases, which will be demonstrated by a phase I clinical trial dedicated to women in resort situations.

Continued involvement of surgeons and multidisciplinary teams in the design and reporting of trials will streamline their adoption into clinical practice. Surgeons need to remain aware of ongoing systemic therapy trials to appropriately select patients for NST and plan for appropriate post-neoadjuvant surgical care.

P3, N=688, Recruiting, Henan Cancer Hospital | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Similarly, combination of photo/thermal ablation with chemotherapy can act to overcome breast cancer resistance. In this review, we focus on the mechanism of breast cancer resistance and the nanoparticle-based strategies used to combat resistance in breast cancer.

HER2-positive breast cancer exhibited three distinct HR-specific subtypes with varying clinical manifestations and treatment responses. These findings suggest personalized treatment strategies considering ER and PR expression patterns, emphasizing the need for further investigations to unravel molecular traits underlying HER2-positive breast cancer with distinct HR expression patterns.

Available evidence supports the efficacy of T-DXd in patients with any history of IHC 1+ or IHC 2+/ISH- scores; however, future research may further refine the population who could benefit from T-DXd or other HER2-directed therapies and identify novel methods for patient identification. Because HER2 expression can change with disease progression or treatment, and variability exists in scoring and interpretation of HER2 status, careful re-evaluation in certain scenarios may help to identify more patients who may benefit from T-DXd.

A multivariable analysis revealed a significant dependence of survival probability on receptor status, general condition, and number of metastatic sites, as well as the time between initial breast cancer diagnosis and the diagnosis date of MBC in months. In sum, OS of patients with MBC has improved continuously and significantly in routine care over the last 27 years.

This study demonstrated that HER2-low tumor may exhibit prognostic significance. The innovative mNeo-Bioscore, based on a new classification of HER2 status, may serve as a prognostic staging system superior to Neo-Bioscore.

In this review, we analyze the biology of HR-positive/HER2-positive breast cancer and summarize the evidence concerning the standard of care options both in neoadjuvant/adjuvant settings and in advanced disease. Additionally, we focus on new trials and drugs for HR-positive/HER2-positive breast cancer and the new entity: HER2-low breast cancer.

Synergies between MELK inhibition with 4OH-tamoxifen (Tam) and ALK inhibition with HER2 inhibitors revealed potential therapeutic avenues for ERα-positive/PR-positive/HER2-negative and ERα-positive/PR-negative/HER2-positive tumors, respectively. Our findings propose MELK as a promising target for ERα-positive/PR-positive/HER2-negative BC and highlight ALK as a potential focus for ERα-positive/PR-negative/HER2-positive BC. The synergistic anti-proliferative effects of MELK with Tam and ALK with HER2 inhibitors underscore kinase inhibitors' potential for selective treatment in diverse BC subtypes, paving the way for personalized and effective therapeutic strategies in BC management.

P3, N=817, Recruiting, SWOG Cancer Research Network | Trial completion date: Jan 2029 --> Jan 2030 | Trial primary completion date: Jan 2029 --> Jan 2030

The incidence of new AA also decreased with subsequent draws in the TN and HER2+ cohorts (TN: 25% to 0-9%, HER2 + : 38% to 14-15%). While the incidence of new AA in serial cfDNA decreased with subsequent draws across all MBC subtypes, new alterations with a potential impact on treatment selection continued to emerge, particularly for patients with HR+/HER2- MBC.

In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly] for a total of four 21-day cycles before surgery. In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification.

Towards this, the rL-A9 peptide was conjugated with the chemotherapeutic drug doxorubicin (DOX) through a N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker...This data was further validated by confocal microscopy, where the fluorescent signal ascertained nuclear accumulation of rL-A9-DOX. The present studies highlight the promising potential of rL-A9-DOX for targeted delivery of the drug into a defined group of cancer cells.

P=N/A, N=58, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Mar 2024 | Trial primary completion date: Nov 2024 --> Mar 2024

The combination of neoadjuvant trastuzumab and pertuzumab with chemotherapy showed good efficiency, and the toxic side effects were tolerable in patients with BC. In cases where pCR was not achieved after neoadjuvant therapy, downregulation of HER2 and Ki-67 expressions was observed.

P3, N=557, Active, not recruiting, Daiichi Sankyo | Trial completion date: Mar 2024 --> Oct 2025